Caldeira J C, Franci C R
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Brain Res Bull. 2000 Aug;52(6):483-9. doi: 10.1016/s0361-9230(00)00284-7.
The cellular organization of the paraventricular nucleus (PVN) is complex and eight distinct regions have been identified by Nissl staining. Three consist of magnocellular neurons and five of parvocellular neurons. Ibotenic acid, a glutamate analogue, is a toxin with neuroexcitatory properties which acts on N-methyl-D-aspartate and metabotropic receptors. Depending on the dose used, ibotenic acid causes extensive damage of parvocellular neurons of the paraventricular nucleus but preserves magnocellular neurons and passage fibers, in contrast to electrolytic lesions, which causes diffuse and nonspecific destruction. We studied the prolactin (PRL) and corticosterone secretion in response to acute stress induced by exposure to the ether, 3 weeks after selective neurotoxic lesion of parvocellular neurons of the paraventricular nucleus by microinjection of ibotenic acid. There was no significant difference in the basal levels of PRL and corticosterone between control and lesioned animals. The plasma PRL increased in the sham and lesioned groups after stress of similar manner. However, the increase in plasma corticosterone in response to stress was significantly higher in lesioned animals. In conclusion, the selective lesion of parvocellular neurons of the PVN did not change basal or stress induced PRL secretion but it caused hypersensitivity of the hypothalamus-pituitary-adrenal axis 3 weeks later, probably by corticotropin releasing hormone (CRH) from hypothalamic areas others than parvocellular neurons of the PVN; hypersensitivity of corticotropes to the secretagogues others than CRH; or hyperresponsiveness of AVP receptors in the adenohypophysis. Furthermore, we cannot rule out a putative inhibitory factor of the hypothalamus-pituitary axis produced by parvocellular neurons of the PVN. This factor modulator of corticotropin secretion could be absent after recuperation of the response of the hypothalamus-pituitary axis to the stress.
室旁核（PVN）的细胞组织很复杂，通过尼氏染色已识别出八个不同区域。其中三个区域由大细胞神经元组成，五个区域由小细胞神经元组成。鹅膏蕈氨酸是一种谷氨酸类似物，是一种具有神经兴奋特性的毒素，作用于N-甲基-D-天冬氨酸和促代谢型受体。根据使用剂量的不同，鹅膏蕈氨酸会对室旁核的小细胞神经元造成广泛损伤，但与电解损伤不同，它能保留大细胞神经元和传导纤维，电解损伤会导致弥漫性和非特异性破坏。我们在通过微量注射鹅膏蕈氨酸对室旁核小细胞神经元进行选择性神经毒性损伤3周后，研究了暴露于乙醚诱导的急性应激下催乳素（PRL）和皮质酮的分泌情况。对照组和损伤组动物的PRL和皮质酮基础水平没有显著差异。假手术组和损伤组在应激后血浆PRL以相似方式升高。然而，损伤组动物对应激的血浆皮质酮升高明显更高。总之，PVN小细胞神经元的选择性损伤并未改变基础或应激诱导的PRL分泌，但在3周后导致下丘脑-垂体-肾上腺轴超敏，这可能是由于室旁核小细胞神经元以外的下丘脑区域释放促肾上腺皮质激素释放激素（CRH）；促肾上腺皮质激素细胞对CRH以外的促分泌素超敏；或腺垂体中血管加压素受体反应过度。此外，我们不能排除PVN小细胞神经元产生的下丘脑-垂体轴假定抑制因子。这种促肾上腺皮质激素分泌的调节因子在下丘脑-垂体轴对应激反应恢复后可能不存在。
